Quantitative intravital microscopy of hepatic transport

IntraVital ◽  
2012 ◽  
Vol 1 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Clifford M. Babbey ◽  
Jennifer C. Ryan ◽  
Erin M. Gill ◽  
Marwan S. Ghabril ◽  
Courtney R. Burch ◽  
...  
Keyword(s):  
Intravital Microscopy ◽  
Hepatic Transport

scholarly journals Quantitative Kinetic Models from Intravital Microscopy: A Case Study Using Hepatic Transport

2019 ◽  
Vol 123 (34) ◽  
pp. 7302-7312 ◽  
Author(s):  
Meysam Tavakoli ◽  
Konstantinos Tsekouras ◽  
Richard Day ◽  
Kenneth W. Dunn ◽  
Steve Pressé
Keyword(s):  
Intravital Microscopy ◽  
Kinetic Models ◽  
Hepatic Transport

scholarly journals Effects of chronic kidney disease on liver transport: quantitative intravital microscopy of fluorescein transport in the rat liver

2014 ◽  
Vol 307 (12) ◽  
pp. R1488-R1492 ◽  
Author(s):  
Jennifer C. Ryan ◽  
Kenneth W. Dunn ◽  
Brian S. Decker
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intravital Microscopy ◽  
Drug Transport ◽  
Cultured Cells ◽  
Organic Anion ◽  
Hepatic Clearance ◽  
Bile Canaliculi ◽  
Hepatic Transport

Clinical studies indicate that hepatic drug transport may be altered in chronic kidney disease (CKD). Uremic solutes associated with CKD have been found to alter the expression and/or activity of hepatocyte transporters in experimental animals and in cultured cells. However, given the complexity and adaptability of hepatic transport, it is not clear whether these changes translate into significant alterations in hepatic transport in vivo. To directly measure the effect of CKD on hepatocyte transport in vivo, we conducted quantitative intravital microscopy of transport of the fluorescent organic anion fluorescein in the livers of rats following 5/6th nephrectomy, an established model of CKD. Our quantitative analysis of fluorescein transport showed that the rate of hepatocyte uptake was reduced by ∼20% in 5/6th nephrectomized rats, consistent with previous observations of Oatp downregulation. However, the overall rate of transport into bile canaliculi was unaffected, suggesting compensatory changes in Mrp2-mediated secretion. Our study suggests that uremia resulting from 5/6th nephrectomy does not significantly impact the overall hepatic clearance of an Oatp substrate.

scholarly journals 77286 Intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis

2021 ◽  
pp. 1-2
Author(s):  
Emmanuel Gabriel ◽  
Minhyung Kim ◽  
Daniel Fisher ◽  
Catherine Mangum ◽  
Kristopher Attwood ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Intravital Microscopy ◽  
Tumor Vasculature

scholarly journals A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emmanuel M. Gabriel ◽  
Minhyung Kim ◽  
Daniel T. Fisher ◽  
Catherine Mangum ◽  
Kristopher Attwood ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Neoadjuvant Therapy ◽  
Anticancer Agents ◽  
Intravital Microscopy ◽  
Pilot Trial ◽  
Oncologic Outcomes ◽  
Tumor Control ◽  
Systemic Delivery ◽  
Tumor Microvasculature ◽  
Lower Blood

AbstractAberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC). During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).

scholarly journals Intravital microscopy imaging of kidney injury and regeneration

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yue Liu ◽  
Zongjin Li
Keyword(s):  
Cell Fate ◽  
Intravital Microscopy ◽  
Single Cells ◽  
Elevated Serum ◽  
Kidney Injury ◽  
Lineage Tracing ◽  
Tissue Slices ◽  
Microscopy Imaging ◽  
Two Photon Microscopy ◽  
Nitrogen Levels

AbstractAcute kidney injury (AKI) is a common clinical symptom, which is mainly manifested by elevated serum creatinine and blood urea nitrogen levels. When AKI is not repaired in time, the patient is prone to develop chronic kidney disease (CKD). The kidney is composed of more than 30 different cells, and its structure is complex. It is extremely challenging to understand the lineage relationships and cell fate of these cells in the process of kidney injury and regeneration. Since the 20th century, lineage tracing technology has provided an important mean for studying organ development, tissue damage repair, and the differentiation and fate of single cells. However, traditional lineage tracing methods rely on sacrificing animals to make tissue slices and then take snapshots with conventional imaging tools to obtain interesting information. This method cannot achieve dynamic and continuous monitoring of cell actions on living animals. As a kind of intravital microscopy (IVM), two-photon microscopy (TPM) has successfully solved the above problems. Because TPM has the ability to penetrate deep tissues and can achieve imaging at the single cell level, lineage tracing technology with TPM is gradually becoming popular. In this review, we provided the key technical elements of lineage tracing, and how to use intravital imaging technology to visualize and quantify the fate of renal cells.

Sex Differences of Hepatic Conjugation of Bilirubin Determine its Maximal Biliary Excretion in Non-Anaesthetized Male and Female Rats

1983 ◽  
Vol 64 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Maurizio Muraca ◽  
Jan De Groote ◽  
Johan Fevery
Keyword(s):  
Biliary Excretion ◽  
High Performance ◽  
Relative Proportion ◽  
Female Rats ◽  
Male Rats ◽  
Transferase Activity ◽  
Hepatic Transport ◽  
Male And Female Rats ◽  
Udp Glucuronosyltransferase ◽  
Rate Limiting

1. Hepatic bilirubin UDP-glucuronosyltransferase activity was higher in female than in male rats; gonadectomy decreased enzyme activity in females and increased it in males. This sex difference in bilirubin conjugation was further used to evaluate the effect of differences in conjugation on the maximal biliary excretion of bilirubin in the non-anaesthetized rat. 2. After infusion of bilirubin, the maximal biliary excretory rate (Tm) and maximal concentration of bilirubin in bile were respectively 70% and 40% higher in female than in male rats; these values were decreased in females after ovariectomy and increased in males after orchiectomy. A linear relationship was found (r = 0.86; P < 0.001) between bilirubin Tm and hepatic bilirubin UDP-glucuronosyltransferase activity in the four groups of rats, suggesting that conjugation was the rate-limiting step for the maximal hepatic transport of bilirubin. 3. At the end of bilirubin infusion, bilirubin conjugates in serum, determined by alkaline methanolysis and high-performance liquid chromatography, ranged from 0.5 to 1.4% of total bilirubin. Therefore no significant reflux of conjugated bilirubin occurred during saturation of the hepatic transport of the pigment, once more suggesting that the secretory step was not rate-limiting. 4. The composition of bilirubin conjugates in bile was similar in the four groups of rats, despite significant differences in transferase activity. This suggests that the relative proportion of bilirubin mono- and di-conjugates in bile is affected by factors other than transferase activity alone. Relatively more monoconjugates were excreted under the bilirubin load than in basal conditions.

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